Amphetamines Hit Men Harder

BALTIMORE - Amphetamines produce a bigger bang in men than women, according to researchers here.

Action Points

Advise patients that this study suggests men respond to amphetamines differently than women, and men may be at a greater risk of amphetamine abuse than women.

BALTIMORE - Amphetamines produce a bigger bang in men than women, according to researchers here.

In a study that measured responses to an amphetamine, men's brains released nearly three times the dopamine of women's brains, reported Gary S. Wand, M.D., a Johns Hopkins endocrinologist, and colleagues in the Journal of Biological Psychiatry published online.

Men also reported more intense positive subjective reactions to the drug, Dr. Wand and colleagues found.

The study included 28 male and 15 female healthy volunteers ages 18 to 29. The investigators used positron emission tomography (PET), in combination with a radiolabeled drug with an affinity for the dopamine receptor, to measure dopamine binding potential and dopamine release in response to an amphetamine in the volunteers' brains.

The investigators focused on the striatum, an area of the brain known to be important in the reward system and addictive behavior.

The study found no significant difference in dopamine binding potential between the sexes. However, dopamine release in response to an amphetamine was 2.6 times higher on average in the men (P=.049).

Dopamine release was significantly higher in three of the four areas of the striatum examined-the anterior putamen, the anterior caudate nuclei, and the posterior caudate nuclei-but not the in the posterior putamen.

At regular intervals after receiving the amphetamine, volunteers were asked to verbally rate their subjective responses to the drug on a five-point scale. Men consistently reported more intense positive reactions, such as feeling high or liking the drug, than women (P=.008).

"These appear to be the first clinical studies whose results may help explain why we see a greater number of men abusing amphetamines than women," Dr Wand said. A 2003 survey conducted by the Substance Abuse and Mental Health Services Administration found that 6% of males but only 3.8% of females 12 and older reported illegal amphetamine use, he noted.

"It remains unclear how male sex accounts for greater dopamine responses to amphetamine throughout the striatum but most likely relates to the influence of sex hormones on the dopaminergic system," the authors said.

Previous studies have suggested that estrogen but not testosterone can reduce dopamine release in response to amphetamines, they noted. The current study, which also measured levels of volunteer's sex hormone, failed to find a link between either sex hormone or dopamine release. However, estrogen levels did correlate with reduced dopamine binding potential in some of the women.

"The difference between estrogen and testosterone may explain why estrogen plays a neuroprotective role in modulating the effects of stimulants on the central nervous system," the authors concluded.

"The finding of robust dopamine release in men could account for their increased vulnerability to stimulant use disorders and methamphetamine toxicity and indicate that future studies need to control for sex," the authors concluded.

The findings might one day lead to drug abuse treatments that are tailored to the sexes, Dr. Wand speculated.

The study might also help researchers learn more about the sexual differences related to neuropsychiatric diseases that involve the striatum, including Parkinson's disease, schizophrenia, Huntington's disease, obsessive compulsive disorder, and Tourette syndrome, Dr. Wand suggested.

The authors noted several weaknesses of this investigation.

They said the order of the scans was not counterbalanced because the placebo scan always preceded the amphetamine scan.

"Although the study was adequately powered for a meaningful comparison between men and women, the relatively small number of women in the luteal phase of the cycle precludes definitive statements about dopamine release as a function of menstrual cycle phase," they wrote

Finally, they wrote, the increases in dopamine concentrations that occur following amphetamine administration probably result from several different mechanisms. These include dopamine reuptake blockade, reverse transport of dopamine through the dopamine transporter as well as possible actions on endogenous opioid systems. "Our use of the term 'dopamine release,' therefore, does not convey a full description of the mechanisms by which amphetamine alters dopamine concentration."

Reviewed by Zalman S. Agus, MD Emeritus Professor at the University of Pennsylvania School of Medicine

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